Figure 3.

Interactions between brain endogenous ouabain, the central renin-angiotensin system, and circulating marinobufagenin in the pathogenesis of salt-sensitive hypertension. In salt-loaded Dahl salt-sensitive rats, sodium retention occurs because renal sodium transport is impaired. Sodium retention stimulates the release of endogenous ouabain in the hippocampus, hypothalamus and pituitary. Brain endogenous ouabain stimulates the RAS in the hypothalamus and pituitary, which activates the SNS. These events stimulate the RAS in the adrenal cortex, and activate adrenocortical production of marinobufagenin. Marinobufagenin, a natriuretic and a vasoconstrictor, induces natriuresis via inhibition of the renotubular Na⁺/K⁺-ATPase. Excessive release of marinobufagenin leads to inhibition of the Na⁺/K⁺-ATPase in vascular smooth muscle cells—which potentiates vasoconstriction—and in the heart—which increases cardiac contractility—causing hypertension. Abbreviations: Na⁺/K⁺-ATPase, sodium/potassium-transporting ATPase; RAS, renin-angiotensin system; SNS, sympathetic nervous system.